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. 2022 Nov 10:12:1038925.
doi: 10.3389/fonc.2022.1038925. eCollection 2022.

SKA1/2/3 is a biomarker of poor prognosis in human hepatocellular carcinoma

Guo-Qiang Song  1 , Tian-Li He  2 , Ke-Jie Ji  1 , Yi-Meng Duan  2 , Jia-Wen Zhang  1 , Guo-Qiang Hu  1   3
Affiliations

SKA1/2/3 is a biomarker of poor prognosis in human hepatocellular carcinoma

Guo-Qiang Song et al. Front Oncol. .

Abstract

Background: Spindle and kinetochore-associated complex subunits 1-3 (SKA1-3) stabilize the kinetochore-attached spindle microtubules in metaphase. Due to the dysregulation in multiple cancers, SKA1-3 is considered a predictor for the prognosis of the patients. However, the potential clinical applications of SKA1-3, particularly in hepatocellular carcinoma (HCC) prognosis and progression, have completely unknown yet.

Methods: For the analysis of SKA1-3 expression and applications in clinics in HCC patients, several databases, such as STRING, UALCAN, GEO, and TCGA, were searched. In addition, the underlying mechanisms of SKA for the regulation of HCC occurrence, development, and progression were also explored.

Results: Compared to the normal controls, HCC patients showed dramatically elevated SKA1-3 expression at the mRNA level, and the values of the area under the curve (AUC) were 0.982, 0.887, and 0.973, respectively. Increased SKA1-3 expression levels were associated with the clinical stage, age, body mass index, tumor grade, tissue subtype, and Tp53 mutation status in HCC patients. The analyses of Kyoto Encyclopedia of Genes and Genome (KEGG) and Gene ontology (GO) demonstrated that SKA1-3 are enriched mainly in the Fanconi anemia, homologous recombination, spliceosome, DNA replication, and cell cycle signaling pathways. The hub genes, such as CDK1, CCNB1, CCNA2, TOP2A, BUB1, AURKB, CCNB2, BUB1B, NCAPG, and KIF11, were identified in protein-protein interactions (PPIs). The expression levels of hub genes were increased in HCC patients and predictive of a poor prognosis. Finally, the expression levels of SKA1-3 were determined using the GEO database.

Conclusions: SKA1-3 are potential prognostic biomarkers of and targets for HCC. In addition, SKA1-3 may affect HCC prognosis via the Fanconi anemia pathway, homologous recombination, spliceosome, DNA replication, and cell cycle signaling pathway.

Keywords: bioinformatics analysis; biomarker; enrichment analysis; liver hepatocellular carcinoma; spindle and kinetochore-associated complex subunit (SKA).

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
The SKA1/2/3 expression levels in different types of human cancers. (A) SKA1, (B) SKA2 (C) SKA3 (ns, p≥0.05 *P<0.05, **P<0.01, ***P<0.001).
Figure 2
Figure 2
The expression of SKA1/2/3 in HCC in TGCA. SKA, spindle and kinetochore-associated; HCC, Hepatocellular carcinoma; the cancer genome atlas, TGCA (ns, p≥0.05, ***P<0.001).
Figure 3
Figure 3
Expression of SKA1/2/3 in cBioPortal database in HCC patients; SKA, spindle and kinetochore-associated; HCC, Hepatocellular carcinoma.
Figure 4
Figure 4
Expression of SKA1/2/3 in TGCA database. (A) is SKA1, (B) is SKA2, (C) is SKA3 SKA1/2/3, spindle and kinetochore associated complex subunit 1/2/3; AUC, area under curve; Cl, confidence level.
Figure 5
Figure 5
The relationship of SKA1 (A), SKA2 (B), SKA3 (C) with OS in HCC patients in TGCA database. SKA, spindle and kinetochore associated; OS, overall survive.
Figure 6
Figure 6
The top 10 genes with positive and negative co-expression of SKA1 (A), SKA2 (B), SKA3 (C) in TCGA database according to Heat map and Venn map. (D) Intersection co-expression genes of SKA1/2/3. Note: |r| >0.4 and P<0.001. SKA, spindle and kinetochore associated. ***P<0.001.
Figure 7
Figure 7
GO analysis of SKA1 (A), SKA2 (B), SKA3 (C) co-expression genes, and intersection co-expression genes among with SKA1/2/3 (D). GO, Gene ontology.
Figure 8
Figure 8
KEGG pathway enrichment analysis of SKA1 (A), SKA2 (B), SKA3 (C) co-expression genes, and intersection co-expression genes among with SKA1/2/3 (D). SKA, spindle and kinetochore associated complex subunit. KEGG, Kyoto Encyclopedia of Genes and Genome.
Figure 9
Figure 9
Hub gene expression was increased in HCC in TGCA database. The expressions of CDK1, CCNB1, CCAN2, TOP2A, BUB1, AURKB, CCNB2, BUB1B, NCAPG, and KIF11 were shown. ***P<0.001.
Figure 10
Figure 10
The hub gene related to the overall survival (OS) of HCC patients in TGCA database. The expressions of CDK1 (A). CCNB1 (B), CCAN2 (C), TOP2A (D), BUB1 (E), AURKB (F), CCNB2 (G), BUB1B (H), NCAPG (I), and KIF11 (J) were shown.
Figure 11
Figure 11
The hub gene related to the disease specific survival (DSF) of HCC patients in TGCA database. The expressions of CDK1 (A). CCNB1 (B), CCAN2 (C). TOP2A (D), BUB1 (E), AURKB (F), CCNB2 (G), BUBIB (H), NCAPG (I), and KIF11 (J) were shown.
Figure 12
Figure 12
The expression of SKA1 (A), 2 (B), 3 (C) in HCC patients in GEO database (GSE 884402). (*P<0.05, **P<0.01, ***P<0.001).
See this image and copyright information in PMC

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